| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Major Depressive Disorder (MDD) |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025463 |
| E.1.2 | Term | Major depressive disorder, single episode |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to evaluate the efficacy of 3 fixed doses of Lu AA21004 (1, 5 and 10 mg once daily) versus placebo after 8 weeks of treatment in subjects with MDD. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To evaluate the efficacy of Lu AA21004 (1, 5 and 10 mg daily) compared with placebo during the 8-week, double-blind treatment.
• To evaluate the proportion of subjects who respond to Lu AA21004 during the 8-week treatment period.
• To evaluate the proportion of subjects who are in remission after 8 weeks of treatment with Lu AA21004 compared with placebo.
• To evaluate the effect of Lu AA21004 on assessments of depression, anxiety, quality of life, and disability.
• To evaluate the effects of Lu AA21004 on healthcare resource utilization.
• To evaluate the population pharmacokinetics of Lu AA21004 and its metabolites Lu AA34443 and Lu AA39835 in subjects with MDD.
• To evaluate the safety and tolerability of Lu AA21004 (1, 5 and 10 mg daily) compared with placebo during the course of treatment.
Exploratory Objective:
• To assess the treatment effect (Lu AA21004 or placebo) on suicidal ideation and behavior.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria:
1. The subject suffers from a major depressive episode (MDE) as the primary diagnosis according to DSM-IV-TR criteria (classification code 296.xx).
2. The reported duration of the current MDE is at least 3 months.
3. The subject has a MADRS total score ≥26.
4. The subject is a man or woman aged between 18 and 75 years, inclusive.
5. The subject is capable of understanding and complying with protocol requirements.
6. A male subject, or a female subject of childbearing potential, who is sexually active agrees to use adequate contraception from Screening throughout the duration of the study and for 1 month after the last dose of study medication. Women NOT of childbearing potential are defined as those who have been surgically sterilized (documented hysterectomy, bilateral oophorectomy and/or tubal ligation) or who are postmenopausal (defined as at least 2 years without menses). (Acceptable methods of contraception are defined in the Contraception and Pregnancy Avoidance Procedure section of the protocol, Section 9.1.10.)
7. The subject has signed the Informed Consent Form. No study-related procedures may be performed before the subject has signed the form. |
|
| E.4 | Principal exclusion criteria |
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. The subject has received any investigational compound <30 days before Screening or 5 half-lives prior to Screening.
2. The subject has received Lu AA21004 in a previous clinical study.
3. The subject is a study-site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee involved in conduct of this study.
4. The subject has 1 or more the following:
a) Any current psychiatric disorder other than MDD as defined in the DSM-IV-TR (as
assessed by the Mini International Neuropsychiatric Interview [MINI]).
b) Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.
c) Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. (Subject must have negative urine drug screen prior to Baseline).
d) Presence or history of a clinically significant neurological disorder (including epilepsy).
e) Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc).
f) Any Axis II disorder that might compromise the study.
5. The subject is required to take excluded medications or it is anticipated that the subject will require treatment with at least 1 of the disallowed concomitant medications during the study (please refer to Excluded Medications, Section 7.3).
6. If female, the subject is pregnant or lactating.
7. The subject has a significant risk of suicide according to the investigator’s opinion or has a score ≥5 on item 10 (suicidal thoughts) of the MADRS or has made a suicide attempt in the previous 6 months.
8. The current depressive symptoms of the subject are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each.
9. The subject has received electroconvulsive therapy within 6 months prior to Screening.
10. The subject is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
11. The subject has a clinically significant unstable illness, for example hepatic impairment or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, rheumatologic, immunologic, infectious, skin and subcutaneous tissue disorder or metabolic disturbance).
12. The subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level >1.5 times the upper limit of normal (xULN).
13. The subject has a serum creatinine level >1.5 xULN.
14. The subject has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
15. The subject has clinically significant abnormal vital signs as determined by the investigator.
16. The subject has 1 or more laboratory value outside the normal range, based on the blood or urine samples taken at the Screening Visit, that are considered by the investigator to be clinically significant.
17. The subject has a thyroid stimulating hormone (TSH) value outside the normal range at the Screening Visit and is deemed clinically significant by the investigator in consultation with the Medical Monitor.
18. The subject has an abnormal electrocardiogram (ECG) as determined by the central reader and confirmed as clinically significant by the investigator and the central reader.
19. The subject has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy.
20. The subject, in the opinion of the investigator, is unlikely to comply with the clinical study protocol or is unsuitable for any reason.
21. The subject has previously participated in this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint for this study is the least squares (LS) mean change from Baseline in the 24-item Hamilton Depression Scale (HAM-D 24) total score after 8 weeks of treatment.
Secondary Endpoints
Secondary efficacy endpoints for this study are:
• LS mean change from baseline HAM-D 24 total score at each week assessed.
• Response rates at each week assessed, with response defined as a ≥50% decrease in the HAM-D 24 total score from Baseline.
• Sustained response from Week 1 for Lu AA21004 compared with placebo, with sustained response defined as at least a 20% decrease from Baseline in HAM-D 24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from baseline at Week 8.
• Remission rates at Week 8, with remission defined as a MADRS total score ≤10.
• LS mean change from Baseline in MADRS total score, Hamilton Anxiety Scale (HAM-A) total score, Clinical Global Impression Scale-Global Improvement (CGI-I), Clinical Global Impression Scale-Severity of Illness (CGI-S), and Hospital Anxiety and Depression (HAD) scale at all study visits where rated.
Pharmacoeconomic Assessments:
The following will be evaluated:
• Medical Outcomes Study (MOS) Short-Form 36 (SF-36), each of the 8 subscales separately.
• Sheehan Disability Scale (SDS).
• Healthcare resource utilization as assessed by the Health Economic Assessment (HEA) Questionnaire. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 16 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 18 |
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